IDENTIFICATION OF CHEMICAL RESPIRATORY ALLERGENS - DOSE-RESPONSE RELATIONSHIPS IN THE MOUSE IGE TEST

A mouse IgE test for the prospective identification of chemical respir atory allergens has been proposed previously. In this method, respirat ory sensitizing potential is measured as a function of induced changes in the serum concentration of IgE following topical exposure of mice to the test material. In previous studies, changes in serum IgE were m easured after treatment of mice with only a single concentration of ch emical. The purpose of the investigations reported here was to examine dose-response relationships in the mouse IgE test with both chemical respiratory allergens and chemicals considered not to cause pulmonary hypersensitivity. The respiratory sensitizers examined were toluene di isocyanate (TDI), diphenylmethane-4,4'-diisocyanate (MDI), hexamethyle ne diisocyanate (HDI), and trimellitic anhydride (TMA), all of which a re known to cause occupational respiratory allergy in a proportion of exposed individuals. Results were compared with those obtained with 2, 4-dinitrochlorobenzene (DNCB) and oxazolone, two contact allergens kno wn or suspected not to cause sensitization of the respiratory tract. I n each case, induced changes in serum IgE were measured under conditio ns of exposure, with respect to application concentrations, where all chemicals elicited positive responses in the local lymph node assay pr ovoking lymphocyte hyperplasia in lymph nodes draining the site of tre atment. In the mouse IgE test, exposure to TDI, MDI, HDI, and TMA in e ach instance caused a substantial dose-related increase in the serum c oncentration of IgE measured 14 days following the initiation of treat ment. In contrast, exposure of mice to the contact allergens DNCB and oxazolone resulted in either no change in serum IgE levels (DNCB) or o nly a comparatively modest increase (oxazolone). These data confirm th at chemical contact and respiratory allergens differ markedly with res pect to the quality of immune response induced in mice and their abili ty to stimulate changes in the serum concentration of IgE. It is propo sed that the mouse IgE test may provide a useful alternative approach to the prospective identification of chemicals that have the ability t o cause sensitization of the respiratory tract.